title: Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy.
abstract: The lysosomal degradation of sulfatide requires the specific enzyme, arylsulfatase A, as well as a heat stable protein called sphingolipid activator protein-1 (SAP-1). While most patients with metachromatic leukodystrophy have defects in arylsulfatase A, some patients have defects in SAP-1. SAP-1 is coded for by a gene on human chromosome 10 that also codes for three other proposed SAP. Examination of the cDNA from two siblings with SAP-1 deficiency revealed a point mutation of nucleotide #650 (counting from the initiation ATG) which is in the SAP-1 coding domain. This C to T transition changed the codon from threonine (ACC) to one coding for isoleucine (ATC). This eliminated the only glycosylation site in mature SAP-1 and could explain the findings made at the protein level.
authors.affiliation: Department of Medicine Medical Genetics, Jefferson Institute of Molecular Medicine, Jefferson Medical College, Philadelphia, PA 19107.
authors.forename: M A
authors.initials: MA
authors.lastname: Rafi
authors.forename: X L
authors.initials: XL
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: DeGala
authors.forename: D A
authors.initials: DA
authors.lastname: Wenger
mesh_terms: D001483:Base Sequence; D006023:Glycoproteins / Q000235:genetics*; D006031:Glycosylation; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D049231:Saposins; D049128:Sphingolipid Activator Proteins
chemical_list: D006023:Glycoproteins; D015345:Oligonucleotide Probes; C483345:PSAP protein, human; D012333:RNA, Messenger; D049231:Saposins; D049128:Sphingolipid Activator Proteins